Cardiovascular diseases, especially various forms of thrombosis, such as coronary, embolic, venous and traumatic thrombosis, account for a large number of death per year. In fact it is estimated by the American Heart Association that 54% of all deaths in the United States can be attributed to cardiovascular disease. It is therefore important for us to be familiar with physical, chemical and clinical aspects of drugs used to treat these form of thrombosis. Since it is believed that initiation of thrombus formation is dependent on platelet aggregation, the inhibitors of platelet aggregation could be prototypes for drugs that are more effectively combat thrombosis that leads to heart attacks and strokes. It was therefore prompted us to search for novel compounds possessing more potent inhibiting activity on platelet aggregation.
Coumarin derivatives such as bishydroxycoumarin and warfarin are the principal anticoagulants. Other clinically useful antiplatelet drugs are aspirin, eicosapentanoic acid (EPA), dipyridamole, dazoxiben, and ticlopidine. Their utilization is, however, limited by the potency and the side effects. This invention describes the preparation of .alpha.-methylene-.gamma.-butyrolactone-containing coumarins, quinolines, and quinolinones from commercially available starting materials in an efficient route. The products describes herein are suitable for large-scale production and exhibit very strong and extensive antiplatelet activity.